Militarinone A, a Neurotrophic Pyridone Alkaloid from Paecilomyces militaris1

Schmidt, Karen; Günther, Wolfgang; Stoyanova, Stefka; Schubert, Barbara; Li, and Zengzhi; Hamburger, Matthias

doi:10.1021/ol016920j

Cited by 92 publications

(103 citation statements)

References 10 publications

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“…These slides were placed in a new 24-well plate, dried, and sterilized under UV-light irradiation for 2 h. NGF-primed PC12 cells were then grown on these slides and incubated for 2 d, fi xed, stained, and examined following known procedures. [ 24,[40][41][42][43] Signifi cantly enhanced neuronal differentiation on the slides coated with compound 1 has been observed, which supported our initial hypothesis ( Figure S1, Supporting Information). The ease and operational simplicity of this coating approach using a solution of the neuritogenic compound and a collagen matrix were found to be appealing.…”

supporting

confidence: 79%

Neuritogenic Surfaces using Natural Product Analogs

Burch

Schmid

Gademann

2014

Adv Healthcare Materials

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supporting

confidence: 79%

Neuritogenic Surfaces using Natural Product Analogs

Burch

Schmid

Gademann

2014

Adv Healthcare Materials

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“…[3,4] Remarkably similar compounds occur in other fungal insect pathogens-for example militarinone A (2) in Paecilomyces militaris. [5] Other 2-pyridones such as leporin A (3) from Aspergillus leporis are known to possess antifeedant properties towards insects. [6] Yet other insect pathogens produce more elaborate 2-pyridones, such as akanthomycin (4) from Akanthomyces gracilis.…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of the 2‐Pyridone Tenellin in the Insect Pathogenic Fungus Beauveria bassiana

et al. 2007

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Genomic DNA from the insect pathogenic fungus Beauveria bassiana was used as a template in a PCR with degenerate primers designed to amplify a fragment of a C-methyl transferase (CMeT) domain from a highly reduced fungal polyketide synthase (PKS). The resulting 270-bp PCR product was homologous to other fungal PKS CMeT domains and was used as a probe to isolate a 7.3-kb fragment of genomic DNA from a BamH1 library. Further library probing and TAIL-PCR then gave a 21.9-kb contig that encoded a 12.9-kb fused type I PKS-NRPS ORF together with ORFs encoding other oxidative and reductive enzymes. A directed knockout experiment with a BaR cassette, reported for the first time in B. bassiana, identified the PKS-NRPS as being involved in the biosynthesis of the 2-pyridone tenellin. Other fungal PKS-NRPS genes are known to be involved in the formation of tetramic acids in fungi, and it thus appears likely that related compounds are precursors of 2-pyridones in fungi. B. bassiana tenellin KO and WT strains proved to be equally pathogenic towards insect larvae; this indicated that tenellin is not involved in insect pathogenesis.

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“…We recently identified a novel fungal alkaloid, militarinone A (MILI A) (Fig. 1 ), in the screening of natural products for neuritogenic properties in PC12 cells [6–8]. Given that MILI A was the first representative of a new chemical class of neurotrophic compounds, we decided to analyze in more detail the signal transduction pathways underlying its effects in PC12 cells.…”

Section: Introductionmentioning

confidence: 99%

Militarinone A induces differentiation in PC12 cells via MAP and Akt kinase signal transduction pathways

2004

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The fungal metabolite militarinone A (MILI A) promotes neurite outgrowth in PC12 cells. This study was conducted to investigate the signaling pathways involved in the cellular differentiation processes induced by the compound, with a focus on cascades implicated with nerve growth factor (NGF)-mediated neuritogenesis. MILI A possessed pronounced amphiphilic properties. The compound rapidly accumulated in the cell membrane and was slowly released into the cytoplasma. In primed PC12 cells, an early activation of protein kinase B (Akt), representing a downstream target of phosphoinositol 3 (PI 3 ) kinase, and a delayed phosphorylation of extracellular signalregulated kinases 1 and 2 (ERK1/2), and of transcription factor cAMP responsive element binding protein (CREB) was found. The NGF-dependent activation of c-Jun amino terminal kinase (SAPK/JNK1) was potentiated. Morphological differentiation of cells and the phosphorylation of specific signal molecules were blocked by the MAP kinase (MEK1) inhibitor PD098059, the PI 3 -kinase (PI 3 K) inhibitor wortmannin and the adenylyl cyclase inhibitor 9-cyclopentyladenine.

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Militarinone A, a Neurotrophic Pyridone Alkaloid from Paecilomyces militaris¹

Cited by 92 publications

References 10 publications

Neuritogenic Surfaces using Natural Product Analogs

Neuritogenic Surfaces using Natural Product Analogs

Biosynthesis of the 2‐Pyridone Tenellin in the Insect Pathogenic Fungus Beauveria bassiana

Militarinone A induces differentiation in PC12 cells via MAP and Akt kinase signal transduction pathways

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